serA2 Resolved · high auto-curated
H37Rv Rv0728c · MTBC0 mtbc0_000770 ·
326 aa · 824689–825669 (-) ·
RefSeq NP_215242.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-3-phosphoglycerate dehydrogenase SerA |
|---|---|
| MTBC0 PGAP re-annotation | D-3-phosphoglycerate dehydrogenase SerA |
| Revised (this work) | D-3-phosphoglycerate dehydrogenase SerA. Pfam: 2-Hacid_dh (PF00389.37), 2-Hacid_dh_C (PF02826.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6WZ71
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible D-3-phosphoglycerate dehydrogenase SerA2 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismH Coenzyme transport and metabolism
|
|---|---|
| Preferred name | serA2 |
| eggNOG description | Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family |
| Orthologous group | COG0111 |
| EC number |
EC 1.1.1.399, EC 1.1.1.95
|
| KEGG orthology |
K00058
|
| KEGG pathways |
map00260, map00680, map01100, map01120, map01130, map01200, map01230
|
| KEGG modules |
M00020
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 2.275 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (157) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
2-Hacid_dh | PF00389.37 | 3.4e-11 | 43–320 | D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain |
2-Hacid_dh_C | PF02826.26 | 1.4e-52 | 115–288 | D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fucA (L-fuculose phosphate aldolase FucA), high confidence from genomic context alone (score 964 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0884c serC |
phosphoserine aminotransferase | 992 | 977 | coexpression:728 database:900 textmining:698 |
Rv0727c fucA |
L-fuculose phosphate aldolase FucA | 965 | 964 ctx | neighborhood:882 coexpression:608 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 944 | 939 | database:900 |
Rv2996c serA1 |
D-3-phosphoglycerate dehydrogenase | 937 | 921 | database:900 |
Rv0729 xylB |
D-xylulose kinase XylB | 903 | 899 ctx | neighborhood:790 cooccurence:467 |
Rv0730 |
GCN5-like N-acetyltransferase | 605 | 605 ctx | neighborhood:601 |
Rv0708 rplP |
50S ribosomal protein L16 | 570 | 570 | experimental:446 |
Rv1295 thrC |
threonine synthase | 606 | 561 | coexpression:474 |
Rv0719 rplF |
50S ribosomal protein L6 | 538 | 539 | experimental:533 |
Rv1286 cysC |
adenylyl-sulfate kinase | 597 | 501 | coexpression:501 |
Rv1294 thrA |
homoserine dehydrogenase | 553 | 499 | coexpression:418 |
Rv2540c aroF |
chorismate synthase | 515 | 494 | coexpression:420 |
Rv0726c |
S-adenosylmethionine-dependent methyltransferase | 481 | 481 ctx | neighborhood:478 |
Rv2785c rpsO |
30S ribosomal protein S15 | 480 | 481 | experimental:446 |
Rv3443c rplM |
50S ribosomal protein L13 | 479 | 479 | experimental:446 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: D-3-phosphoglycerate dehydrogenase SerA
- MTBC0 PGAP product: D-3-phosphoglycerate dehydrogenase SerA
- Pfam (hmmscan --cut_ga): 2-Hacid_dh PF00389.37 (E=3e-11), 2-Hacid_dh_C PF02826.26 (E=1e-52)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215242.1)
- Domains: Pfam-A via hmmscan --cut_ga — 2-Hacid_dh (PF00389.37), 2-Hacid_dh_C (PF02826.26)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0111 - Curated reference: UniProt I6WZ71 (TrEMBL, unreviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
76 functional partner(s); context anchor
fucA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000770|Rv0728c|serA2 MTPRPRALVTAPLRGPGFAQLRRLADVVYDPWIDQRPLRIYSAEQLADRITAVAADVLVVESDSVGGPVFERGLRVVAATRGDPSNVDIPGATAAGIPVLHTPARNADAVAEMTVALLLAVARHLIPADADVRSGNIFRDGTIPYQRFRGAEIAGLTAGLVGLGAVGRAVRWRLSGLGLRVIAHDPYRDDAGHSLDELLAEADIVSMHAAVTDDTIGMIGAQQFAAMRDGAVFLNTARSQLHDTDALVDALRGGKLAAAGLDHFTGEWLPTDHPLVSMPNVVLTPHIGGATWNTEARQARMVADDLGALLSGNRPAHVVNPEVLGS